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Generated: November 20, 2017

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Title:Polymer conjugates of opioid antagonists
Abstract: The invention provides polymer conjugates of opioid antagonists comprising a polymer, such as poly(ethylene glycol), covalently attached to an opioid antagonist. The linkage between the polymer and the opioid antagonist is preferably hydrolytically stable. The invention also includes a method of treating one or more side effects associated with the use of opioid analgesics, such as constipation, nausea, or pruritus, by administering a polymer conjugate of the invention.
Inventor(s): Bentley; Michael David (Huntsville, AL), Roberts; Michael James (Williamsburg, VA), Shen; Xiaoming (Madison, AL), Cheng; Lin (Huntsville, AL)
Assignee: Nektar Therapeutics (San Francisco, CA)
Filing Date:Oct 06, 2009
Application Number:12/574,335
Claims:1. A pharmaceutical composition comprising a polymer conjugate; an opioid agonist; and a pharmaceutically acceptable carrier, wherein the polymer conjugate has the formula: ##STR00009## or pharmaceutically acceptable salt thereof, wherein: Y is allyl; Z is OH; X is --NHC(O)--, --NH--, --OC(O)NH--, --O--, --S-- or --NHC(O)NH--; and POLY is methoxy poly(ethylene glycol), wherein POLY has a molecular weight of from about 100 Da to about 800 Da; and wherein the pharmaceutical composition is formulated into a form suitable for oral administration.

2. The pharmaceutical composition of claim 1, wherein the opioid agonist is selected from the group consisting of alfentanil, bremazocine, buprenorphine, butorphanol, codeine, cyclazocine, dezocine, diacetylmorphine, dihydrocodeine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine (pethidine), methadone, morphine, nalbuphine, noscapine, oxycodone, oxymorphone, papaverine, pentazocine, pethidine, phenazocine, propiram, propoxyphene, sufentanil, thebaine and tramadol.

3. The pharmaceutical composition of claim 1, wherein POLY has a molecular weight of from about 100 Da to about 500 Da.

4. The pharmaceutical composition of claim 1, wherein X is --O--.
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